ORCID Profile
0000-0003-1835-8679
Current Organisation
Women's and Children's Hospital
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.PREGHY.2016.04.008
Abstract: Pre-ecl sia is a serious complication of pregnancy and contributes to maternal and offspring mortality and morbidity. Randomised controlled trials evaluating therapeutic interventions for pre-ecl sia have reported many different outcomes and outcome measures. Such variation contributes to an inability to compare, contrast, and combine in idual studies, limiting the usefulness of research to inform clinical practice. The development and use of a core outcome set would help to address these issues ensuring outcomes important to all stakeholders, including patients, will be collected and reported in a standardised fashion. An international steering group including healthcare professionals, researchers, and patients, has been formed to guide the development of this core outcome set. Potential outcomes will be identified through a comprehensive literature review and semi-structured interviews with patients. Potential core outcomes will be entered into an international, multi-perspective online Delphi survey. All key stakeholders, including healthcare professionals, researchers, and patients will be invited to participate. The modified Delphi method encourages whole and stakeholder group convergence towards consensus 'core' outcomes. Once core outcomes have been agreed upon it is important to determine how they should be measured. The truth, discrimination, and feasibility assessment framework will assess the quality of potential outcome measures. High quality outcome measures will be associated with core outcomes. Mechanisms exist to disseminate and implement the resulting core outcome set within an international context. Embedding the core outcome set within future clinical trials, systematic reviews, and clinical practice guidelines could make a profound contribution to advancing the usefulness of research to inform clinical practice, enhance patient care, and improve maternal and offspring outcomes. The infrastructure created by developing a core outcome set for pre-ecl sia could be leveraged in other settings, for ex le selecting research priorities and clinical practice guideline development. PROSPECTIVE REGISTRATION: [1] Core Outcome Measures in Effectiveness Trials (COMET) registration number: 588. [2] International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD42015015529.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Elsevier BV
Date: 10-2018
Publisher: Wiley
Date: 07-2013
DOI: 10.1111/TRF.12221
Publisher: BMJ
Date: 11-08-2015
DOI: 10.1136/ARCHDISCHILD-2014-306945
Abstract: In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH. Eighty-three infants ≤30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3. Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life. Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH.
Publisher: Wiley
Date: 20-06-2023
DOI: 10.1111/IMM.13674
Abstract: A significant number of babies present transiently with low protein kinase C zeta (PKCζ) levels in cord blood T cells (CBTC), associated with reduced ability to transition from a neonatal Th2 to a mature Th1 cytokine bias, leading to a higher risk of developing allergic sensitisation, compared to neonates whose T cells have ‘normal’ PKCζ levels. However, the importance of PKCζ signalling in regulating their differentiation from a Th2 to a Th1 cytokine phenotype propensity remains undefined. To define the role of PKCζ signalling in the regulation of CBTC differentiation from a Th2 to a Th1cytokine phenotype we have developed a neonatal T cell maturation model which enables the cells to develop to CD45RA − /CD45RO + T cells while maintaining the Th2 immature cytokine bias, despite having normal levels of PKCζ. The immature cells were treated with phytohaemagglutinin, but in addition with phorbol 12‐myristate 13‐acetate (PMA), an agonist which does not activate PKCζ. This was compared to development in CBTC in which the cells were transfected to express constitutively active PKCζ. The lack of PKCζ activation by PMA was monitored by western blot for phospho‐PKCζ and translocation from cell cytosol to the membrane by confocal microscopy. The findings demonstrate that PMA fails to activate PKCζ in CBTC. The data show that CBTC matured under the influence of the PKC stimulator, PMA, maintain a Th2 cytokine bias, characterised by robust IL‐4 and minimal interferon gamma production (IFN‐γ), and lack of expression of transcriptional factor, T‐bet. This was also reflected in the production of a range of other Th2/Th1 cytokines. Interestingly, introduction of a constitutively active PKCζ mutant into CBTC promoted development towards a Th1 profile with high IFN‐γ production. The findings demonstrate that PKCζ signalling is essential for the immature neonatal T cells to transition from a Th2 to a Th1 cytokine production bias.
Publisher: Wiley
Date: 20-01-2016
Publisher: Elsevier BV
Date: 04-2013
DOI: 10.1016/J.PLACENTA.2013.01.013
Abstract: The beneficial effects of antenatal glucocorticoid therapy on fetal lung maturation require their passage across the placental glucocorticoid barrier, composed of glucocorticoid metabolising enzymes, such as 11 beta hydroxysteroid dehydrogenase (11βHSD), and proteins that efflux glucocorticoids, such as P-glycoprotein (P-gp). We have shown that 11βHSD2 activity is responsive to antenatal glucocorticoids, however the effect on placental P-gp remains unknown. Since antenatal glucocorticoids have a greater prophylactic effect in females compared to males, we also assessed whether this therapy induced sexually dimorphic effects on P-gp expression, as well as on placental inflammatory processes mediated by corticosteroids. Placentas were collected from 53 women presenting in threatened preterm labour, and processed to assess cytokine and P-gp mRNA expression, as well as P-gp localisation using immunohistochemistry. Placental cytokine, P-gp mRNA and protein expression were not altered by timing of antenatal glucocorticoids or fetal sex. However, both P-gp mRNA and protein expression were significantly reduced in placentas from infants born small for gestational age (SGA) compared to appropriately grown infants (p < 0.05), suggesting a role for P-gp in its pathogenesis via the provision of a net increase in fetal exposure to bioactive exogenous glucocorticoids. While this study identified no change in placental P-gp following antenatal glucocorticoids, it has provided evidence that P-gp plays an important role in cases of SGA. This supports the known mechanistic relationship between antenatal glucocorticoids, fetal development and the postnatal phenotype. Given that P-gp also confers fetal protection from a number of drugs, this finding warrants further investigation to improve clinical management of the SGA fetus.
Publisher: BMJ
Date: 15-04-2015
DOI: 10.1136/ARCHDISCHILD-2014-307565
Abstract: Elevated cerebral fractional tissue oxygen extraction (cFTOE ≥0.4) predicts early brain injury in very preterm infants. While blood transfusion increases oxygen-carrying capacity, its ability to improve cerebral oxygen kinetics in the immediate newborn period remains unknown. To investigate the effect of red blood cell (RBC) transfusion in the first 24 h of life on cFTOE in infants ≤29 weeks gestation. cFTOE was calculated from cerebral tissue oxygenation index (TOI) and cutaneous oximetry measured over a 30 min epoch before and after transfusion. Infants were dichotomised according to pre-transfusion cFTOE (low <0.4 vs high ≥0.4). 24 babies were included, 12 in each group. Pre- and post-transfusion Hb were similar between the groups. cFTOE significantly reduced after transfusion in the high but not low-extraction group (p<0.01). Early RBC transfusion favourably alters cerebral oxygen kinetics in infants with elevated cFTOE, showing potential for modification of the risk of hypoxic (brain) injury.
Publisher: Elsevier BV
Date: 11-2019
Publisher: Springer Science and Business Media LLC
Date: 24-10-2012
DOI: 10.1038/PR.2012.144
Publisher: Frontiers Media SA
Date: 28-01-2022
Publisher: AMPCo
Date: 09-2014
DOI: 10.5694/MJA13.11142
Abstract: To assess the impact of Aboriginal status, active cigarette smoking and smoking cessation during pregnancy on perinatal outcomes. Retrospective cohort study from 1 January 1999 to 31 December 2008. All singleton births in South Australia. Population-based birth records of pregnancies to Aboriginal women (n = 4245) and non-Aboriginal women (n = 167 746). Adjusted odds ratios (aORs) and 95% CIs for adverse maternal and neonatal outcomes according to Aboriginal status and maternal smoking in pregnancy. Active cigarette smoking during pregnancy was associated with an increased risk of adverse perinatal outcomes, including premature labour (Aboriginal, 1-10 cigarettes per day: aOR, 1.69 95% CI, 1.28-2.23 non-Aboriginal, 1-10 cigarettes per day: aOR, 1.46 95% CI, 1.34-1.58), preterm birth (Aboriginal, 1-10 cigarettes per day: aOR, 1.40 95% CI, 1.14-1.73 non-Aboriginal, 1-10 cigarettes per day: aOR, 1.48 95% CI, 1.39-1.57), intrauterine growth restriction (Aboriginal, 1-10 cigarettes per day: aOR, 2.33 95% CI, 1.77-3.08 non-Aboriginal, 1-10 cigarettes per day: aOR, 2.65 95% CI, 2.48-2.83) and small for gestational age (Aboriginal, 1-10 cigarettes per day: aOR, 2.49 95% CI, 2.06-3.00 non-Aboriginal, 1-10 cigarettes per day: aOR, 2.29 95% CI, 2.20-2.40). For both Aboriginal and non-Aboriginal women who smoked 11 or more cigarettes per day the aOR for these outcomes increased. Smoking cessation in the first trimester reduced these risks to levels comparable with non-smokers. The risk of each adverse outcome was greater in Aboriginal than non-Aboriginal women for all smoking categories however, interactions between Aboriginal status and smoking were not significant, indicating an equal contribution of smoking to poor outcomes in both populations. Smoking cessation or reduction during pregnancy would significantly improve outcomes in both Aboriginal and non-Aboriginal women. This should be made a clear priority to improve pregnancy outcomes for all women.
Publisher: Elsevier BV
Date: 2022
DOI: 10.1016/J.FERTNSTERT.2021.08.030
Abstract: To determine the proportion of pregnancies resulting in birth that were conceived with the use of clomiphene citrate (CC) and the frequency of multiple pregnancy. Whole-of-population cohort study, constructed through data linkage. Comprehensive Australian Government records of dispensed medications were linked to state Perinatal Registry records for all births of at least 20 weeks' gestation. The state of South Australia. Women who maintained pregnancy for at least 20 weeks and gave birth between July 2003 and December 2015, a total of 150,713 women with 241,561 pregnancies. Not applicable. Ongoing pregnancy occurring in proximity to CC, defined as dispensing from 90 days before to the end of a conception window derived from newborn date of birth and gestational age. Linkage to dispensed prescription records was achieved for 97.9% of women. Women who conceived with CC tended to be older and socioeconomically advantaged and more likely than other women to have a history of miscarriage. Ongoing pregnancies associated with CC comprised 1.6% of the total 5.7% were multiple births (mostly twins, 94.6%) compared with 1.5% in the remainder (98.5% twins). In South Australia, 1.6% of pregnancies (1 in 60) of at least 20 weeks' gestation were conceived proximal to CC dispensing. Of these, 5.7% were multiple pregnancies. This takes the proportion of women who achieved an ongoing pregnancy with medical assistance from 4.4%, based on reports from assisted reproductive technology clinics, to 6% in total.
Publisher: Springer Science and Business Media LLC
Date: 18-05-2015
DOI: 10.1038/PR.2015.96
Abstract: The underlying neuro-protective mechanisms of antenatal magnesium sulfate (MgSO(4)) in infants born preterm remain poorly understood. Early neonatal brain injury may be preceded by low cerebral blood flow (CBF) and elevated cerebral fractional tissue oxygen extraction (cFTOE). This study investigated the effect of antenatal MgSO(4) on cerebral oxygen delivery, consumption, and cFTOE in preterm infants. CBF and tissue oxygenation index were measured, and oxygen delivery, consumption, and cFTOE calculated within 24 h of birth and at 48 and 72 h of life in 36 infants ≤ 30 wk gestation exposed to MgSO(4) and 29 unexposed infants. Total internal carotid blood flow and cerebral oxygen delivery did not differ between the groups at the three study time-points. Cerebral oxygen consumption and cFTOE were lower in infants exposed to antenatal MgSO(4) (P = 0.012) compared to unexposed infants within 24 h of delivery. This difference was not evident by 48 h of age. Fewer infants in the MgSO(4) group developed P/IVH by 72 h of age (P = 0.03). Infants exposed to MgSO(4) had similar systemic and cerebral hemodynamics but lower cFTOE compared to nonexposed. These findings suggest reduced cerebral metabolism maybe a component of the neuro-protective actions of antenatal MgSO(4).
Publisher: Wiley
Date: 2022
DOI: 10.1002/CTI2.1377
Abstract: Transfusion with washed packed red blood cells (PRBCs) may be associated with reduced transfusion‐related pro‐inflammatory cytokine production. This may be because of alterations in recipient immune responses. This randomised trial evaluated the effect of transfusion with washed compared with unwashed PRBCs on pro‐inflammatory cytokines and endothelial activation in 154 preterm newborns born before 29 weeks’ gestation. Changes in plasma cytokines and measures of endothelial activation in recipient blood were analysed after each of the first three transfusions. By the third transfusion, infants receiving unwashed blood had an increase in IL‐17A ( P = 0.04) and TNF ( P = 0.007), whereas infants receiving washed blood had reductions in IL‐17A ( P = 0.013), TNF ( P = 0.048), IL‐6 ( P = 0.001), IL‐8 ( P = 0.037), IL‐12 ( P = 0.001) and IFN‐γ ( P = 0.001). The magnitude of the post‐transfusion increase in cytokines did not change between the first and third transfusions in the unwashed group but decreased in the washed group for IL‐12 ( P = 0.001), IL‐17A ( P = 0.01) and TNF ( P = 0.03), with the difference between the groups reaching significance by the third transfusion ( P 0.001 for each cytokine). The pro‐inflammatory immune response to transfusion in preterm infants can be modified when PRBCs are washed prior to transfusion. Further studies are required to determine whether the use of washed PRBCs for neonatal transfusion translates into reduced morbidity and mortality.
Publisher: Bioscientifica
Date: 09-2013
DOI: 10.1530/REP-13-0239
Abstract: Docosahexaenoic acid (DHA) supplementation in pregnancy may confer some clinical benefits however, this compound can exert pro-oxidant effects. In this study, we investigated the effects of DHA on pro-oxidant/antioxidant balance in term and preterm placental explants, assessing oxidative stress marker concentrations, antioxidant capacity and pro-inflammatory cytokine production. Term ( n =8) and preterm ( n =9) placental explants were exposed to lipopolysaccharide (LPS, 1 ng/ml), DHA (1, 10 and 100 μM), and DHA and LPS simultaneously or pre-treated with DHA for 24 h prior to LPS treatment. The production of malondialdehyde (MDA, lipid peroxidation), 8-hydroxy-2-deoxy guanosine (8-OHdG, oxidative DNA damage) and pro-inflammatory cytokines (tumour necrosis factor α (TNFα), interleukin 6 and interferon-γ) and total antioxidant capacity were measured. DHA at a concentration of 100 μM induced oxidative stress in term placentas, while at all the three concentrations, it induced oxidative stress in preterm placentas. DHA and LPS resulted in reduced MDA levels in term ( P .005) and preterm ( P =0.004) placentas and reduced 8-OHdG levels in preterm placentas ( P =0.035). DHA pre-treatment, but not co-treatment with LPS, reduced 8-OHdG levels ( P .001) in term placentas. DHA increased antioxidant capacity only in term placentas ( P .001), with lower antioxidant capacity being observed overall in preterm placentas compared with term placentas ( P ≤0.001). In term placentas, but not in preterm ones, DHA co-treatment and pre-treatment reduced LPS-induced TNFα levels. The ability of DHA to alter placental pro-oxidant/antioxidant balance is dependent on the DHA concentration used and the gestational age of the placental tissue. DHA has a greater capacity to increase oxidative stress in preterm placentas, but it offers greater protection against inflammation-induced oxidative stress in term placentas. This appears to be a result of DHA altering placental antioxidant capacity. These data have implications for the timing and concentration of DHA supplementation in pregnancy.
Publisher: Wiley
Date: 08-02-2019
DOI: 10.1111/JPC.14402
Abstract: Anaemia of prematurity will affect 90% of all very preterm infants, resulting in at least one red blood cell (RBC) transfusion. A significant proportion of preterm infants require multiple transfusions over the course of hospital admission. Growing evidence supports an association between transfusion exposure and adverse neonatal outcomes. In adults, transfusion-associated sepsis, transfusion-related acute lung injury and haemolytic reactions are the leading causes of transfusion-related morbidity and mortality however, these are seldom recognised in newborns. The association between transfusion and adverse outcomes remains inconclusive. However, the evidence from preclinical studies demonstrates that RBC products can directly modulate immune cell function, a pathway termed transfusion-related immunomodulation (TRIM), which may provide a mechanism linking transfusion exposure with neonatal morbidities. Finally, we discuss the impact of TRIM on transfusion medicine, how we may address these issues and the emerging areas of research aimed at improving the safety of transfusions in this vulnerable population.
Publisher: Wiley
Date: 15-10-2019
DOI: 10.1111/JPC.14644
Publisher: Massachusetts Medical Society
Date: 30-03-2017
Publisher: BMJ
Date: 16-08-2011
Publisher: Informa UK Limited
Date: 09-2011
DOI: 10.1586/ECI.11.51
Abstract: Maternal infection and inflammation are common events during pregnancy. This article documents evidence that suggests such inflammation compromises the development of the fetal innate immune response, in support of an in utero origins hypothesis of neonatal and childhood inflammatory disease. The potential for this response to exhibit sex specificity is also explored, based on evidence of sexually dimorphic placental responses to maternal inflammation.
Publisher: Wiley
Date: 05-12-2022
DOI: 10.1002/HPJA.686
Abstract: To raise expectant fathers' awareness of risk factors for stillbirth. A set of brief text messages was developed addressing recognised risk factors for stillbirth: avoidance of maternal cigarette smoking, maternal going to sleep on side messaging, awareness of the importance of noticing and reporting changes in foetal movement and fathers' involvement in shared decision making for timing of birth. Eight messages were inserted into the SMS4dads pilot program being conducted by NSW Health. Feedback on the messages was requested. Participants rated the quality of the messages on a three‐point Likert scale and provided comments. Overall, 2528 messages were sent to 626 fathers' mobile phones, 45% of fathers replied with 666 ratings and 115 comments evaluating the texts. The quantitative ratings indicated substantial overall approval of the messages. Within the coding category “Evaluation of Message Content,” three themes described fathers' reactions and feelings about the smoking, movement, side sleeping and birth timing messages: “important‐good information,” “not appropriate/anxiety provoking” and “not relevant‐obvious.” Three themes reflecting the attributes of the messages within the “Service Quality” category were “need more information,” “complements public health” and “child voice fit.” Results indicate that the messages are an acceptable way to provide information and suggested actions addressing stillbirth risk factors to fathers‐to‐be. Fathers' awareness of the risk factors for stillbirth can assist mothers to take appropriate actions for a healthy birth. Information on risk factors can be provided to fathers via a father‐focused text messaging service.
Publisher: AMPCo
Date: 26-02-2018
DOI: 10.5694/MJA17.01287
Publisher: Wiley
Date: 04-06-2022
DOI: 10.1111/JPC.16030
Publisher: Wiley
Date: 21-10-2014
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.PLACENTA.2011.08.010
Abstract: Glucocorticoids (GC) are known to influence fetal ROS production and anti-oxidant defences yet little attention has focused on the potential for effects in the placenta. We hypothesised that antenatal GC exposure alters placental pro-oxidant-anti-oxidant balance sex-specifically, based upon the known relationship between male sex and poor pregnancy outcome. Placentae were collected from 60 women who delivered between 24 and 31 completed weeks gestation and placental oxidative and nitrative stress (protein carbonyl, lipid hydroperoxide, and nitrotyrosine concentration) and anti-oxidant enzyme activity (glutathione peroxidase, thioredoxin reductase, and superoxide dismutase) measured. A pro-oxidant state was observed in placentae of male compared to female infants born within 72 h of antenatal GC exposure, with higher levels of protein carbonyl content (p = 0.04), lipid hydroperoxide (p < 0.01) and nitrotyrosine content (p = 0.02), and lower levels of glutathione peroxidase activity (p = 0.01). A pro-oxidant state continued to be observed in placentae of males compared to females born outside of 72 h, with higher protein carbonyl content (p = 0.04) and lower glutathione peroxidase activity (p = 0.01) than females, however no differences in placental lipid hydroperoxide and nitrotyrosine content were observed. These sex-specific alterations in products of placental oxidative stress could not purely be explained by differences in clinical illness severity (CRIB2 score). Therefore, these sex-specific alterations in placental pro-oxidant-antioxidant balance in response to antenatal betamethasone exposure, independent of illness severity, could contribute to the patho-physiologic processes underlying oxygen radical diseases of the newborn, conditions known to exhibit a male excess.
Publisher: Elsevier BV
Date: 2012
Publisher: Wiley
Date: 21-06-2020
Publisher: Wiley
Date: 14-05-2020
DOI: 10.1111/MICC.12622
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.PLEFA.2015.04.003
Abstract: Thirty one infants born less than 30 weeks׳ gestational age were randomised to receive either 40 (n=11), 80 (n=9) or 120 (n=11) mg/kg/day of docosahexaenoic acid (DHA) respectively as an emulsion, via the feeding tube, commenced within 4 days of the first enteral feed. Twenty three infants were enroled in non-randomised reference groups n=11 who had no supplementary DHA and n=12 who had maternal DHA supplementation. All levels of DHA in the emulsion were well tolerated with no effect on number of days of interrupted feeds or days to full enteral feeds. DHA levels in diets were directly related to blood DHA levels but were unrelated to arachidonic acid (AA) levels. All randomised groups and the maternal supplementation reference group prevented the drop in DHA levels at study end that was evident in infants not receiving supplementation. Australian New Zealand Clinical Trials Registry: ACTRN12610000382077.
Publisher: Cambridge University Press (CUP)
Date: 05-10-2015
DOI: 10.1017/S2040174415007151
Abstract: The objective was to investigate the association between early and late maternal smoking during pregnancy on offspring body mass index (BMI). We undertook a retrospective cohort study using linked records from the Women’s and Children’s Health Network in South Australia. Among a cohort of women delivering a singleton, live-born infants between January 2000 and December 2005 ( n =7658), 5961 reported not smoking during pregnancy, 297 reported quitting smoking during the first trimester of pregnancy, and 1400 reported continued smoking throughout pregnancy. Trained nurses measured the height and weight of the children at preschool visits in a state-wide surveillance programme. The main outcome measure was age- and sex-specific BMI z-score. At 4 to 5 years, mean ( s.d. ) BMI z-score was 0.40 (1.05), 0.60 (1.07) and 0.65 (1.18) in children of mothers who reported never smoking, quitting smoking and continued smoking during pregnancy, respectively. Compared with the group of non-smokers, both quitting smoking and continued smoking were associated with an increase in child BMI z-score of 0.15 (95% confidence interval: 0.01–0.29) and 0.21 (0.13–0.29), respectively. A significant dose–response relationship was also observed between the number of cigarettes smoked per day on average during the second half of pregnancy and the increase in offspring BMI z-score ( P .001). In conclusion, any maternal smoking in pregnancy, even if mothers quit, is associated with an increase in offspring BMI at 4 to 5 years of age.
Publisher: European Respiratory Society (ERS)
Date: 30-07-2013
DOI: 10.1183/09031936.00054913
Abstract: Does cigarette smoking in pregnancy explain the increased risk of adverse perinatal outcomes that occur with maternal asthma or does it compound the effect? Using population based birth records, a retrospective analysis was conducted of all singleton pregnancies in South Australia over 10 years (1999-2008 n=172 305), examining maternal asthma, cigarette smoking and quantity of smoking to estimate odds ratios. Compared with nonasthmatic females who did not smoke during pregnancy, both asthmatic females who smoked and those who did not smoke during pregnancy had a significantly increased risk of gestational diabetes, antepartum haemorrhage, polyhydramnios, premature rupture of membranes, emergency Caesarean section, and the child being small for gestational age and having congenital abnormalities. These associations suggest that asthma, independently of maternal smoking, increases the risk of these adverse perinatal outcomes. Maternal smoking was itself associated with an increased risk of a number of poor neonatal outcomes, with a dose-response relationship observed. Notably, maternal asthma combined with cigarette smoking significantly increased the risk of preterm birth and urinary tract infections to a greater degree than with either exposure alone. Maternal asthma and cigarette smoking during pregnancy are both independently associated with adverse perinatal outcomes and, combined, compound the risk of preterm birth and urinary tract infections.
Publisher: Wiley
Date: 2020
DOI: 10.1002/CTI2.1121
Publisher: Elsevier BV
Date: 09-2016
Publisher: Wiley
Date: 25-07-2020
DOI: 10.1111/TRF.15952
Publisher: Informa UK Limited
Date: 18-04-2011
DOI: 10.3109/14767058.2011.569618
Abstract: Dysregulated vascular resistance contributes to hypotension following preterm birth with sex-specific differences in microvascular function conferring a male disadvantage. We hypothesized that glucocorticoid mediated, sex-specific differences in the endogenous catecholamine norepinephrine and endothelially derived endothelin-1 (ET-1) contribute to microvascular dysfunction in preterm neonates in the immediate newborn period. Umbilical and plasma ET-1 and normetanephrine, in 24 h urine s les, were determined at 24, 72, and 120 h of age in 24-34 week infants (n = 60). Microvascular blood flow was determined by laser Doppler flowmetry. In infants born within 72 h of antenatal glucocorticoid exposure, normetanephrine was higher in females than males (p = 0.048). Normetanephrine was inversely correlated with both microvascular blood flow at 24 h (p = 0.025) and CRIB II (p = 0.001). While umbilical arterial ET-1 was higher in females delivered <72 h after antenatal betamethasone (p = 0.006), plasma ET-1 did not correlate with microvascular blood flow or illness severity. Only sex and normetanephrine contributed significantly to both microvascular blood flow and endothelium dependant vasodilatation. These data support glucocorticoid mediated, sex-specific differences in mediators of vascular tone that may contribute to the impaired mechanisms compromising successful hemodynamic adaption to neonatal life and resulting in excess male morbidity and mortality.
Publisher: Informa UK Limited
Date: 03-2020
DOI: 10.2147/DDDT.S239704
Publisher: BMJ
Date: 23-01-2023
DOI: 10.1136/ARCHDISCHILD-2022-324531
Abstract: To evaluate the association of donor sex with transfusion-associated recipient immune responses in preterm newborns receiving unwashed and washed blood. A cohort study using data collected during the Effect of Washed versus Unwashed Packed Red Blood Cell Transfusion on Immune Responses in the Extremely Preterm Newborn randomised trial. Participants were recruited from two South Australian hospitals between September 2015 and December 2020. Preterm newborns ( weeks). Transfusion with unwashed and washed packed red blood cells (PRBCs) from either exclusively male or any female donor for the first three transfusions. The primary outcome was the change from baseline in post-transfusion plasma cytokine concentrations, specifically interferon gamma, interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12, IL-17A and tumour necrosis factor (TNF). In total, 153 newborns were evaluated. By the third transfusion, the magnitude of pretransfusion to post-transfusion change in cytokines between the groups differed for IL-6 (p=0.003), IL-12 (p=0.008), IL-17A (p=0.003) and TNF (p=0.007). On post hoc comparison, compared with the unwashed–any female donor group, IL-6 (p .05), IL-12 (p .05) and IL-17A (p .01) were lower in the washed–exclusively male donor group, and IL-6 (p .01), IL-12 (p .05) and TNF (p .01) were lower in the washed–any female donor group. These findings suggest that transfusion with unwashed PRBCs from female donors is associated with an increased recipient immune response, an effect that can be ameliorated with pretransfusion washing. Larger randomised controlled studies confirming this mechanistic link between donor sex and transfusion-associated morbidity are warranted. ACTRN12613000237785.
Publisher: American Physiological Society
Date: 08-2009
DOI: 10.1152/AJPREGU.00175.2009
Abstract: Placental 11β-hydroxysteroid dehydrogenase-2 (11βHSD2) limits fetal glucocorticoid exposure and is associated with physiological stability in the premature newborn infant. Antenatal betamethasone alters 11βHSD2 activity and confers sex-specific advantages in neonatal outcome. We investigated the influence of betamethasone and sex on 11βHSD2 activity, neonatal adrenal function and clinical course in 24- to 36-wk gestation neonates from birth to day 5 of life. Univariate analyses demonstrated an interaction between timing of betamethasone exposure and sex for 11βHSD2 activity rate ( P = 0.02) and umbilical arterial cortisol ( P = 0.01). For infants born 72 h following antenatal betamethasone, females had higher 11βHSD2 activity ( P 0.01) and umbilical arterial cortisol ( P = 0.01) than males. Females born 72 h of betamethasone exposure had higher day 1 urinary cortisol, if exposed to perinatal stress, than males ( P 0.01). For infants born 72 h after betamethasone exposure, 11βHSD2 activity was negatively correlated with Clinical Illness Severity Score score ( r = −0.79 P = 0.01) and positively correlated with mean arterial blood pressure ( r = 0.8 P = 0.01) only in females. Sex-specific placental 11BHSD2 autoregulation following antenatal betamethasone exposure may limit adrenal suppression in females influencing physiological stability following preterm birth. A lack of adjustment in 11βHSD2 and adrenal response may contribute to the increased incidence of poor outcome observed in preterm males.
Publisher: CSIRO Publishing
Date: 2009
DOI: 10.1071/RD08224
Abstract: 5α-Reduced steroids, including allopregnanolone, suppress neuronal activity and can have neuroprotective effects in the fetus. 5α-Reductases in the placenta may contribute precursors to brain allopregnanolone synthesis. Preterm birth and glucocorticoids, administered for fetal lung maturation or for maternal asthma, may influence reductase expression. The aims of the present study were to evaluate placental 5α-reductase isoform expression during late gestation and to examine fetal sex differences and the effects of glucocorticoid therapies on the expression of these enzymes. Expression of the two 5α-reductase isoenzymes was measured in placental s les, whereas cortisol concentrations were measured in cord blood, from two cohorts. The first cohort consisted of women who delivered preterm and received betamethasone treatment (n = 41) the second cohort consisted of women who delivered at term and were either healthy controls (n = 30) or asthmatics who had used glucocorticoids (n = 24). Placental expression of both isoenzymes increased with advancing gestation and there were marked sex differences in levels of 5α-reductase I (P 0.05), but not of 5α-reductase II. The expression of both enzymes was positively correlated with cortisol levels (P 0.05), but there was no effect of recent glucocorticoid exposure. These findings suggest that the preterm neonate may have lower developmental exposure to 5α-reduced steroids and may lack steroid-mediated neuroprotection depending on fetal sex.
Publisher: Wiley
Date: 11-07-2023
DOI: 10.1111/AJO.13719
Abstract: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy liver disease, characterised by pruritus and increased total serum bile acids (TSBA), Australian incidence 0.6–0.7%. ICP is diagnosed by non‐fasting TSBA ≥ 19 μmol/L in a pregnant woman with pruritus without rash without a known pre‐existing liver disorder. Peak TSBA ≥ 40 and ≥ 100 μmol/L identify severe and very severe disease respectively, associated with spontaneous preterm birth when severe, and with stillbirth, when very severe. Benefit‐vs‐risk for iatrogenic preterm birth in ICP remains uncertain. Ursodeoxycholic acid remains the best pharmacotherapy preterm, improving perinatal outcome and reducing pruritus, although it has not been shown to reduce stillbirth.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.PLACENTA.2017.06.009
Abstract: A significant proportion of children born preterm will experience some level of neurodevelopmental impairment. Changes in placental function have been observed with many antenatal conditions that are risk factors for preterm birth and/or poor neurodevelopment including fetal growth restriction and in-utero inflammation. This review will highlight placental factors that have been studied to understand the underlying mechanisms and identify biomarkers that lead to poor child neurodevelopmental outcomes. These include changes in gross morphological and histopathological structure and the placental inflammatory response to prenatal infection. Further, we will describe the placenta's role as both a barrier to maternally-derived bioactive substances critical for normal fetal brain development, such as cortisol, and a source of neuroactive steroids and neurotrophins known to have critical functions in neuronal proliferation, axonal growth, myelination and the regulation of apoptosis. Finally, emerging data supporting the potential utility of novel placental biomarkers in the early prediction of poor neurodevelopmental outcome in infants born both preterm and term will be discussed. These include the assessment of genetic variants (e.g. single nucleotide polymorphisms in placental tissue) and epigenetic biomarkers (e.g. placental microRNAs and placental DNA methylation). With the placenta the key tissue regulating the fetal environment, integration of observed changes in placental function with genetic and epigenetic variations may advance our ability to predict future infant health. Ultimately, this may facilitate targeted allocation of health resources with the aim of improving lifelong neurodevelopmental capability.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.EARLHUMDEV.2016.03.016
Abstract: Neurotrophins are proteins critically involved in neural growth, survival and differentiation, and therefore important for fetal brain development. Reduced cord blood neurotrophins have been observed in very preterm infants (<32weeks gestation) who subsequently develop brain injury. Antenatal steroid exposure can alter neurotrophin concentrations, yet studies to date have not examined whether this occurs in the late preterm infant (33-36weeks gestation), despite increasing recognition of subtle neurodevelopmental deficits in this population. To assess the impact of antenatal steroids on cord blood neurotrophins in late preterm infants following antenatal steroid exposure. Retrospective analysis. Late preterm infants (33-36weeks n=119) and term infants (37-41weeks n=129) born at the Women's and Children's Hospital, Adelaide. Cord blood neurotrophin-3 (NT-3), NT-4, nerve growth factor (NGF) and brain derived neurotrophic factor (BDNF) concentrations measured by ELISA. Cord blood NT-4 and NGF were increased at term compared to the late preterm period (p 24h prior to delivery (p<0.01). This study identified an association between reduced cord blood NT-3 and antenatal steroid exposure in the late preterm period. The reduced NT-3 may be a consequence of steroids inducing neuronal apoptosis, thereby reducing endogenous neuronal NT3 production, or be an action of steroids on other maternal or fetal NT-3 producing cells, which may then affect neuronal growth, differentiation and survival. Regardless of the specific mechanism, a reduction in NT-3 may have long term implications for child neurodevelopment, and emphasizes the ongoing vulnerability of the fetal brain across the full preterm period.
Publisher: Elsevier BV
Date: 08-2010
Publisher: Elsevier BV
Date: 06-2011
DOI: 10.1016/J.PLACENTA.2011.03.004
Abstract: The mechanisms that contribute to adverse outcomes for the neonate in pregnancies complicated by asthma may be mediated via changes in placental immune function. This study was designed to determine whether the presence of maternal asthma during pregnancy alters the placental pro-inflammatory immune response in vitro. A prospective cohort study of women with asthma (n = 22) and control (n = 11) subjects had placentae collected immediately after delivery. Placental explants were exposed to an immune challenge, lipopolysaccharide, in the presence and absence of cortisol in vitro. Cytokines, glucocorticoid receptor α (GR α) and p38 MAPK protein were measured. Placentae of control pregnancies had an increase in pro-inflammatory cytokine production over a 24 h period. Placentae from pregnancies complicated by maternal asthma had a reduced pro-inflammatory cytokine response to an immune challenge relative to the controls especially in relation to the production of interleukin (IL)-1β and TNFα regardless of fetal sex. Cortisol inhibition of placental cytokine production was dependent on timing of exposure, fetal sex and presence and absence of asthma. GRα and p38 MAPK protein expression did not appear to contribute to differences in response to endotoxin or cortisol. Maternal asthma during pregnancy induces a hyposensitive inflammatory state in the placenta which is regulated by cortisol in a sexually dimorphic manner.
Publisher: American Thoracic Society
Date: 15-03-2011
Publisher: Elsevier BV
Date: 07-2020
DOI: 10.1016/J.PREGHY.2020.06.005
Abstract: To develop consensus definitions for the core outcome set for pre-ecl sia. Potential definitions for in idual core outcomes were identified across four formal definition development initiatives, nine national and international guidelines, 12 Cochrane systematic reviews, and 79 randomised trials. Eighty-six definitions were entered into the consensus development meeting. Ten healthcare professionals and three researchers, including six participants who had experience of conducting research in low- and middle-income countries, participated in the consensus development process. The final core outcome set was approved by an international steering group. Consensus definitions were developed for all core outcomes. When considering stroke, pulmonary oedema, acute kidney injury, raised liver enzymes, low platelets, birth weight, and neonatal seizures, consensus definitions were developed specifically for low- and middle-income countries because of the limited availability of diagnostic interventions including computerised tomography, chest x-ray, laboratory tests, equipment, and electroencephalogram monitoring. Consensus on measurements for the pre-ecl sia core outcome set will help to ensure consistency across future randomised trials and systematic reviews. Such standardization should make research evidence more accessible and facilitate the translation of research into clinical practice. Video abstract can be available at: /ftrgvrfu0u9glqd/6.%20Standardising%20definitions%20in%20teh%20pre-ecl sia%20core%20outcome%20set%3A%20a%20consensus%20development%20study.mp4?dl=0.
Publisher: BMJ
Date: 07-2023
Publisher: Wiley
Date: 16-10-2018
DOI: 10.1111/JPC.14260
Abstract: To assess the prevalence, types and indications for fluid bolus therapy in neonates with haemodynamic compromise. This was a pragmatic, international, multicentre observational study in neonatal units across Australasia, Europe and North America with a predefined study period of 10-15 study days per participating neonatal unit between December 2015 and March 2017. Infants ≤28 days of age who received a fluid bolus for the management of haemodynamic compromise (≥10 mL/kg given at ≤6 h) were included. A total of 163 neonates received a bolus over 8479 eligible patient days in 41 neonatal units. Prevalence of fluid bolus therapy varied between centres from 0 to 28.6% of admitted neonates per day, with a pooled prevalence rate of 1.5% (95% confidence interval 1.1-1.9%). The most common fluid used was 0.9% sodium chloride (129/163 79%), and the volume of fluid administered was most commonly 10 mL/kg (115/163 71%) over a median of 30 min (interquartile range 20-60). The most frequent indications were hypotension (n = 56 34%), poor perfusion (n = 20 12%) and metabolic acidosis (n = 20 12%). Minimal or no clinical improvement was reported by clinicians in 66 of 163 cases (40%). Wide international variations in types, indications and effects of fluid bolus administration in haemodynamically compromised neonates suggest uncertainty in the risk-benefit profile. This is likely to reflect the lack of robust evidence to support the efficacy of different fluid types, doses and appropriate indications. Together, these highlight a need for further clinically relevant studies.
Publisher: Wiley
Date: 19-10-2016
DOI: 10.1111/VOX.12442
Publisher: Elsevier BV
Date: 03-2014
DOI: 10.1016/J.JPEDS.2013.10.041
Abstract: To evaluate the relationship between cerebral fractional tissue oxygen extraction (cFTOE), a measure of oxygen delivery-consumption equilibrium, and the risk of early poor outcome in very preterm infants. Cerebral blood flow, tissue oxygenation index (by near-infrared spectroscopy), and arterial oxygen content were measured, and cerebral oxygen delivery, consumption, and cFTOE were calculated at 3 intervals in the first 72 hours of life in infants ≤ 30 weeks gestational age (GA). A receiver operating characteristic curve was derived with an a priori defined dichotomized outcome of good or poor, defined as death or sonographic brain injury (grade ≥ II intraventricular hemorrhage) by day 7. Seventy-one infants were enrolled, with a mean (SD) GA of 27 (2) weeks. cFTOE demonstrated better discrimination for the study outcome at <24 hours of age than at 48 or 72 hours of age (P = .01). The area under the curve for cFTOE at the initial measurement was no different from that for GA alone (0.87 95% CI, 0.77-0.95 vs 0.81 95% CI, 0.69-0.92), but the combined measure of cFTOE and GA had better discrimination (0.96 95% CI, 0.91-1.0) than either cFTOE (P = .03) or GA (P = .016) alone. A cFTOE of 0.4 had a sensitivity of 82% and specificity of 75% for risk of early poor outcome. Elevated cFTOE values are associated with increased risk of early poor outcome in very preterm infants. Its predictive value is further improved with the addition of GA.
Publisher: American Academy of Pediatrics (AAP)
Date: 07-2009
Abstract: OBJECTIVE: With male gender as a strong predictor of cardiovascular instability, we hypothesized that gender-specific differences in circulating carbon monoxide levels contributed to dysregulated microvascular function in preterm male infants. METHODS: Infants born at 24 to 34 weeks of gestation (N = 84) were studied in a regional tertiary neonatal unit. Carboxyhemoglobin levels were measured through spectrophotometry in umbilical arterial blood and at 24, 72, and 120 hours after birth. Microvascular blood flow was determined through laser Doppler flowmetry. RESULTS: Carboxyhemoglobin levels demonstrated a strong inverse relationship with gestational age (r = −0.636 P & .001) and were higher in boys (P = .032). Repeated-measures analysis of variance showed a significant decrease in arterial carboxyhemoglobin levels over time (P & .001), with significant between-subjects effects for gestational age (P = .011) and gender (P = .025). Positive correlations with microvascular blood flow at 24 hours of age (r = 0.495 P & .001) and 120 hours of age (r = 0.548 P & .001) were observed. With controlling for gestational age, carboxyhemoglobin levels at 72 hours were greater for infants who died in the first week of life (P = .035). CONCLUSIONS: The gestational age- and gender-specific differences in carboxyhemoglobin levels and the relationship with dysregulated microvascular blood flow, a state related to greater illness severity and hypotension, are novel findings not confined solely to sick preterm infants. Both inducible heme oxygenase-dependent and non–heme oxygenase-dependent pathways may initially play a central role in carbon monoxide production, inducing pathophysiologic processes in a gender-specific manner.
Publisher: Informa UK Limited
Date: 20-04-2023
Publisher: Wiley
Date: 10-11-2020
DOI: 10.1111/JPC.15273
Publisher: Elsevier BV
Date: 02-2012
DOI: 10.1016/J.PLACENTA.2011.11.005
Abstract: Pregnancy induces a number of alterations to maternal physiology to accommodate the increased demands made by the developing fetus and placenta. These alterations appear at least in part to be driven by products derived from the feto-placental unit, including microchimeric cells, as well as placental exosomes and microparticles, inducing changes to maternal physiology both during pregnancy and beyond. Further, increasing evidence suggests that some of these alterations are dependent on the sex of the fetus. Pre-ecl sia and asthma represent two common pregnancy complications that have provided valuable insight into how the feto-placental unit influences maternal physiology in a sex-specific manner. Pregnancy-induced alterations in maternal physiology may expose pre-existing subclinical pathologies and provide insight into future maternal health and disease. While most pregnancy-induced alterations to the maternal system are reversed following delivery, some can persist after parturition leading to cardiovascular, metabolic and autoimmune disease and increased risk of early mortality.
Publisher: Elsevier BV
Date: 12-2012
DOI: 10.1016/J.PLACENTA.2012.09.010
Abstract: The increase in oxidative stress during pregnancy is associated with increased placental antioxidant enzyme activity and may additionally be limited by the uncoupling proteins (UCPs). There is little data on the expression and localisation of UCP2 in the human preterm placenta or on its role in the regulation of placental oxidative stress. Placentae were collected from women with singleton pregnancies who delivered between 24 and 36 weeks gestation (n = 54) and from a term reference group who delivered following uncomplicated pregnancy (n = 11). UCP2 expression and localisation was determined by quantitative real-time RTPCR using Taqman gene expression assays and immunohistochemistry. Placental lipid hydroperoxide and nitrotyrosine content was determined by ELISA. UCP2 mRNA expression increased from 24 to 41 weeks gestation (p < 0.001) and was positively correlated with placental weight (p = 0.004). While UCP2 expression was lower in small for gestational age infants (p = 0.045) it did not differ with respect to timing of antenatal betamethasone exposure nor with placental lipid hydroperoxide or nitrotyrosine content. UCP2 staining was identified in the cytotrophoblast in 34% of s les and in the syncytiotrophoblast in 63% of s les. Cytotrophoblast staining was more frequent in later gestations (p = 0.03) with syncytiotrophoblast UCP2 staining was not altered by gestation. In the preterm group, no association was observed with time since antenatal betamethasone exposure or placental lipid hydroperoxide or nitrotyrosine content. The current data supports gestation dependant alterations in UCP2 mRNA expression and immunohistochemical localisation in the human placenta but no evidence for an important role for UCP2 in protection against placental oxidative damage.
Publisher: Frontiers Media SA
Date: 03-10-2022
Publisher: Wiley
Date: 05-09-2019
Abstract: To quantify the effect of different methodological decisions on the identification of potential core outcomes to inform the development of recommendations for future core coutcome set developers. Mixed methods study. A core outcome set for pre-ecl sia was used as an exemplar. A long list of potential core outcomes was developed by undertaking a systematic review of pre-ecl sia trials and performing a thematic analysis of in-depth patient interviews. Specific methods used to generate long lists of potential core outcomes were evaluated. Different methodological decisions had a substantial impact on the identification of potential core outcomes. Extracting outcomes from published pre-ecl sia trials was an effective way of identifying 48 maternal, eight fetal, 25 neonatal outcomes, and eight patient-reported outcomes. Limiting the extraction of outcomes to primary outcomes or outcomes commonly reported in pre-ecl sia trials reduced the number and ersity of potential core outcomes identified. Thematic analysis of in-depth patient interviews ensured an additional five patient reported outcomes and six outcomes related to future child health were identified. Future core outcome set developers should use quantitative and qualitative methods when developing a long list of potential core outcomes. TWEETABLE ABSTRACT: @OfficialNIHR research published in @BJOGtweets informs new recommendations for future @coreoutcomes developers.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.MEHY.2018.01.002
Abstract: While normal oxygen saturation is commonly thought to be a marker of normal oxygenation, cutaneous saturation does not account for the sufficiency of oxygen within each cell or that of the system overall. Rather, cutaneous oximetry simply defines the saturation of haemoglobin (Hb) with oxygen in a pulsatile vessel. Assessment of sufficiency is best determined by measurement of the amount of oxygen left over following aerobic respiration. This left over oxygen is 'stored' on Hb in the venous compartment and can be calculated as the venous oxygen content. We hypothesize that the development of a venous oxygen content or saturation reference range in a group of well, uninjured very preterm newborns and subsequent application, in a randomised trial, with a structural, functional and molecular outcome will resolve the method for assessment of oxygen sufficiency in preterms by demonstrating both clinical safety and effectiveness. This method could be subsequently used for titration of supplemental oxygen.
Publisher: MDPI AG
Date: 23-11-2021
Abstract: Cord blood T cells (CBTC) from a proportion of newborns express low/deficient levels of some protein kinase C (PKC) isozymes, with low levels of PKCζ correlating with increased risk of developing allergy and associated decrease in interferon-gamma (IFN-γ) producing T cells. Interestingly, these lower levels of PKCζ were increased/normalized by supplementing women during pregnancy with n-3 polyunsaturated fatty acids. However, at present, we have little understanding of the transient nature of the deficiency in the neonate and how PKCζ relates to other PKC isozymes and whether their levels influence maturation into IFN-γ producing T cells. There is also no information on PKCζ isozyme levels in the T cell subpopulations, CD4+ and CD8+ cells. These issues were addressed in the present study using a classical culture model of neonatal T cell maturation, initiated with phytohaemagglutinin (PHA) and recombinant human interleukin-2 (rhIL-2). Of the isozymes evaluated, PKCζ, β2, δ, μ, ε, θ and λ/ι were low in CBTCs. The PKC isozyme deficiencies were also found in the CD4+ and CD8+ T cell subset levels of the PKC isozymes correlated between the two subpopulations. Examination of changes in the PKC isozymes in these deficient cells following addition of maturation signals showed a significant increase in expression within the first few hours for PKCζ, β2 and μ, and 1–2 days for PKCδ, ε, θ and λ/ι. Only CBTC PKCζ isozyme levels correlated with cytokine production, with a positive correlation with IFN-γ, interleukin (IL)-2 and tumour necrosis factor-alpha (TNF), and a negative association with IL-9 and IL-10. The findings reinforce the specificity in using CBTC PKCζ levels as a biomarker for risk of allergy development and identify a period in which this can be potentially ‘corrected’ after birth.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 16-03-2023
Publisher: Springer Science and Business Media LLC
Date: 12-01-2021
DOI: 10.1186/S12884-020-03481-Y
Abstract: Severe early onset (less than 34 weeks gestation) intrahepatic cholestasis of pregnancy (ICP) affects 0.1% of pregnant women in Australia and is associated with a 3-fold increased risk of stillbirth, fetal hypoxia and compromise, spontaneous preterm birth, as well as increased frequencies of pre-ecl sia and gestational diabetes. ICP is often familial and overlaps with other cholestatic disorders. Treatment options for ICP are not well established, although there are limited data to support the use of ursodeoxycholic acid (UDCA) to relieve pruritus, the main symptom. Rif icin, a widely used antibiotic including in pregnant women, is effective in reducing pruritus in non-pregnancy cholestasis and has been used as a supplement to UDCA in severe ICP. Many women with ICP are electively delivered preterm, although there are no randomised data to support this approach. We have initiated an international multicentre randomised clinical trial to compare the clinical efficacy of rif icin tablets (300 mg bd) with that of UDCA tablets (up to 2000 mg daily) in reducing pruritus in women with ICP, using visual pruritus scores as a measuring tool. Our study will be the first to examine the outcomes of treatment specifically in the severe early onset form of ICP, comparing “standard” UDCA therapy with rif icin, and so be able to provide for the first-time high-quality evidence for use of rif icin in severe ICP. It will also allow an assessment of feasibility of a future trial to test whether elective early delivery in severe ICP is beneficial. Australian New Zealand Clinical Trials Registration Number (ANZCTR): 12618000332224p (29/08/2018). HREC No: HREC/18/WCHN/36. EudraCT number: 2018–004011-44. IRAS: 272398. NHMRC registration: APP1152418 and APP117853.
Publisher: BMJ
Date: 03-2022
Publisher: Wiley
Date: 09-04-2019
DOI: 10.1111/JPC.14473
Publisher: MDPI AG
Date: 17-05-2018
DOI: 10.3390/NU10050634
Publisher: BMJ
Date: 28-09-2020
DOI: 10.1136/ARCHDISCHILD-2020-319804
Abstract: Surfactant is an effective treatment for respiratory distress syndrome, being particularly important for infants in whom continuous positive airway pressure (CPAP) provides insufficient support. Supraglottic airway devices present an attractive option for surfactant delivery, particularly as an alternative to methods dependent on direct laryngoscopy, a procedural skill that is both difficult to learn and in which to maintain competence. Published studies provide encouraging data that surfactant administration by supraglottic airway device can be performed with a high rate of success and may reduce the need for subsequent intubation compared with either continued CPAP or surfactant administration via endotracheal tube. However, existing randomised controlled trials (RCTs) are heterogeneous in design and include just over 350 infants in total. To date, all RCT evidence has been generated in tertiary units, whereas the greatest potential for benefit from the use of these devices is likely to be in non-tertiary settings. Future research should investigate choice and utility of device in addition to safety and effectiveness of procedure. Importantly, studies conducted in non-tertiary settings should evaluate feasibility, meaningful clinical outcomes and the impact that this approach might have on infants and their families. Supraglottic airway devices may represent a simple and effective mode of surfactant administration that can be widely used by a variety of clinicians. However, further well-designed RCTs are required to determine their role, safety and effectiveness in both tertiary and non-tertiary settings before introduction into routine clinical practice.
Publisher: American Academy of Pediatrics (AAP)
Date: 04-2017
Abstract: John Scott Haldane recognized that the administration of supplemental oxygen required titration in the in idual. Although he made this observation in adults, it is equally applicable to the preterm newborn. But how, in practice, can the oxygen requirements in the preterm newborn be determined to avoid the consequences of too little and too much oxygen? Unfortunately, the current generation of oxygen saturation trials in preterm newborns guides saturation thresholds rather than in idual oxygen requirements. For this reason, we propose an alternate model for the description of oxygen sufficiency. This model considers the adequacy of oxygen delivery relative to simultaneous consumption. We describe how measuring oxygen extraction or the venous oxygen reservoir could define a physiologically based definition of adequate oxygen. This definition would provide a clinically useful reference value while making irrelevant the absolute values of both oxygen delivery and consumption. Additional trials to test adjunctive, noninvasive measurements of oxygen status in high-risk preterm newborns are needed to minimize the effects of both insufficient and excessive oxygen exposure.
Publisher: MDPI AG
Date: 16-12-2022
Publisher: Elsevier BV
Date: 07-2015
No related grants have been discovered for michael stark.